Neurological manifestations as primary presentation of COVID-19 in hospitalized patients.

Objective: To characterize patients with coronavirus disease 2019 (COVID-19) who presented primarily with neurologic symptoms without typical COVID-19 symptoms of fever, cough, and dyspnea.

Methods: We retrospectively identified COVID-19-positive patients 18 years and older that had neurology symptoms on presentation requiring neurology consultation between March 14, 2020 and May 18, 2020. The patients were then classified into those with typical COVID-19 symptoms and those without.

An Acute, Severe Axonal Sensorimotor Polyneuropathy in the Setting of Nitrous Oxide Abuse.

Nitrous oxide, often used as an anesthetic agent, is also increasingly a drug of abuse due to its euphoric and anxiolytic effects. Frequent exposure to nitrous oxide can lead to neurologic complications, including B12 deficiency and resultant subacute myeloneuropathy, as well as direct neurotoxicity. A clinical presentation of acute sensorimotor polyneuropathy mimicking Guillain-Barré syndrome after chronic nitrous oxide abuse has been reported only rarely.

Prognostic Significance of Cyclic Seizures in Status Epilepticus.

Purpose: Status epilepticus (SE) is a commonly encountered neurologic condition associated with high mortality rates. Cyclic seizures (CS) are a common form of SE, but its prognostic significance has not been well established. In this retrospective study, the mortality of cyclic versus noncyclic forms (NCSs) of SE are compared.

Large central lumbar disc herniation causing acute cauda equina syndrome with loss of evoked potentials during prone positioning for surgery.

Background: Few studies in the literature discuss operative positioning for lumbar surgery precipitating acute cauda equina syndromes (CES).

Case Description: A 56-year-old male with a large L2-3-disc herniation was placed prone on a Jackson table. He immediately lost all motor and sensory evoked potentials.

Clinical outcomes in patients with generalized periodic discharges.

Purpose: Generalized periodic discharges (GPDs) are frequently identified in the EEGs of hospitalized patients but their prognostic significance remains unclear. We retrospectively reviewed clinical data in patients with GPDs to elucidate factors associated with in-hospital mortality.

Method: We reviewed data from inpatients at three different hospitals affiliated with our institution in whom GPDs were reported on routine EEGs by fellowship-trained electroencephalographers during the years 2010-2012.

Genomic instability causes HGF gene activation in colon cancer cells, promoting their resistance to necroptosis.

Background & Aims: Genomic instability promotes colon carcinogenesis by inducing genetic mutations, but not all genes affected by this process have been identified. We investigated whether genomic instability in human colorectal cancer (CRC) cells produces mutations in the hepatocyte growth factor (HGF) gene.

Methods: We genotyped human colon tumor tissues and adjacent nontumor tissues collected from 78 patients University of Pittsburgh Health Sciences and Veterans Hospital, along with 40 human CRC and adjacent nontumor tissues in a commercial microarray.

Novel Death Defying Domain in Met entraps the active site of caspase-3 and blocks apoptosis in hepatocytes.

Unlabelled: Met, the transmembrane tyrosine kinase receptor for hepatocyte growth factor (HGF), is known to function as a potent antiapoptotic mediator in normal and neoplastic cells. Herein we report that the intracellular cytoplasmic tail of Met has evolved to harbor a tandem pair of caspase-3 cleavage sites, which bait, trap, and disable the active site of caspase-3, thereby blocking the execution of apoptosis. We call this caspase-3 cleavage motif the Death Defying Domain (DDD).

A hepatocyte growth factor receptor (Met)-insulin receptor hybrid governs hepatic glucose metabolism.

Met is the transmembrane tyrosine kinase cell surface receptor for hepatocyte growth factor (HGF) and is structurally related to the insulin receptor (INSR) tyrosine kinase. Here we report that the HGF-Met axis regulates metabolism by stimulating hepatic glucose uptake and suppressing hepatic glucose output. We show that Met is essential for an optimal hepatic insulin response by directly engaging INSR to form a Met-INSR hybrid complex, which culminates in a robust signal output.

The Met protooncogene is a transcriptional target of NF kappaB: implications for cell survival.

NF kappaB transcription factor regulates gene expression in response to extracellular stimuli such as TNF alpha. The genes regulated by NF kappaB encode for proteins which control cell growth and survival. Met is the tyrosine kinase receptor for hepatocyte growth factor, and it too promotes cell mitogenesis and survival.

Somatic mutation and functional polymorphism of a novel regulatory element in the HGF gene promoter causes its aberrant expression in human breast cancer.

The HGF gene is transcriptionally silenced in normal differentiated breast epithelial cells, but its repression fails to occur in mammary carcinoma tissues and cell lines. The molecular mechanisms underpinning aberrant HGF expression in breast cancer cells are unknown. Here we report the discovery of a DNA element located 750 bp upstream from the transcription start site in the human HGF promoter that acts as a transcriptional repressor and is a target of deletion mutagenesis in human breast cancer cells and tissues.

Glutathione peroxidase 3, deleted or methylated in prostate cancer, suppresses prostate cancer growth and metastasis.

Glutathione peroxidase 3 is a selenium-dependent enzyme playing a critical role in detoxifying reactive oxidative species and maintaining the genetic integrity of mammalian cells. In this report, we found that the expression of glutathione peroxidase 3 (GPx3) was widely inactivated in prostate cancers. Complete inactivation of GPx3 correlates with a poor clinical outcome.

Lack of Fas antagonism by Met in human fatty liver disease.

Hepatocytes in fatty livers are hypersensitive to apoptosis and undergo escalated apoptotic activity via death receptor-mediated pathways, particularly that of Fas-FasL, causing hepatic injury that can eventually proceed to cirrhosis and end-stage liver disease. Here we report that the hepatocyte growth factor receptor, Met, plays an important part in preventing Fas-mediated apoptosis of hepatocytes by sequestering Fas. We also show that Fas antagonism by Met is abrogated in human fatty liver disease (FLD).

Promotion of Fas-mediated apoptosis in Type II cells by high doses of hepatocyte growth factor bypasses the mitochondrial requirement.

The death receptor pathway is coupled to the mitochondria apoptosis pathway. However, mitochondrial participation, which is stimulated by Bid but suppressed by Bcl-2/Bcl-x(L), is required in certain cells (Type II), but not in others (Type I). While these differences were originally characterized in the lymphoid cell lines, the typical Type II cells are represented by hepatocytes in vivo.

PI3K is negatively regulated by PIK3IP1, a novel p110 interacting protein.

Signaling initiated by Class Ia phosphatidylinositol-3-kinases (PI3Ks) is essential for cell proliferation and survival. We discovered a novel protein we call PI3K interacting protein 1 (PIK3IP1) that shares homology with the p85 regulatory PI3K subunit. Using a variety of in vitro and cell based assays, we demonstrate that PIK3IP1 directly binds to the p110 catalytic subunit and down modulates PI3K activity.

Hepatocyte growth factor protects against hypoxia/reoxygenation-induced apoptosis in endothelial cells.

Hypoxia/reoxygenation causes cellular injury and death associated with a number of pathophysiological conditions, including myocardial ischemia/reperfusion injury and stroke. The cell death pathways induced by hypoxia/reoxygenation and their underlying regulatory mechanisms remain poorly understood. Recent studies have shown that hypoxia/reoxygenation can induce Bax translocation and cytochrome c release.

Prevention, evaluation, and management of complications following thyroidectomy for thyroid carcinoma.

The rate of complications during thyroid surgery has decreased because of better instrumentation, illumination, and surgical expertise. Despite these improvements, certain patients, those requiring reoperation, those with invasive cancers or with numerous nodal metastasis or recurrent tumors, and those with large substernal goiters have a low but appreciable risk for complications. When planning a thyroid operation, one should perform the operation that corrects these problems and decreases the risk for complications.

A functional polymorphism at the transcriptional initiation site in beta2-glycoprotein I (apolipoprotein H) associated with reduced gene expression and lower plasma levels of beta2-glycoprotein I.

Human beta2-glycoprotein I (beta2GPI), also known as apolipoprotein H, has been implicated in haemostasis and the production of anti-phospholipid antibodies. There is a wide range of interindividual variation in beta2GPI plasma levels that is thought to be under genetic control, but its molecular basis remains unknown. To understand the genetic basis of beta2GPI variation, we analyzed the 5' flanking region of the beta2GPI gene for mutation detection by DHPLC and identified a point mutation at the transcriptional initiation site (-1C-->A) with a carrier frequency of 12.

Hepatocyte growth factor induces Wnt-independent nuclear translocation of beta-catenin after Met-beta-catenin dissociation in hepatocytes.

Hepatocyte growth factor (HGF) and Wnt signaling pathways have been shown to be important in embryogenesis and carcinogenesis. The aim of this study was to elucidate the mechanism of functional similarities observed in the two pathways. We used normal rat liver, primary hepatocyte cultures and a dominant-negative Met expression system to study the effect of HGF on Wnt pathway components.

A mechanism of cell survival: sequestration of Fas by the HGF receptor Met.

Death receptors such as Fas are present in a variety of organs including liver and play an important role in homeostasis. What prevents these harmful receptors from forming homooligomers, clustering, and initiating the apoptotic pathway is not known. Here, we report the discovery of a cell survival mechanism by which Met, a growth factor receptor tyrosine kinase, directly binds to and sequesters the death receptor Fas in hepatocytes.